The objectives of this multidisciplinary Program Project are: (1) to predict human fetal growth and postnatal developmental characteristics of the infant from measures of maternal leukocyte metabolism and nutritional status at midgestation; (2) to differentiate between nutritional, cardiovascular and hormonal influences on fetal development; (3) to identify mechanisms at the molecular level by which nutrients regulate enzyme activities and limit fetal growth; (4) to relate changes in maternal leukocyte metabolism during gestation (used as a model for other rapidly replicating cells) to ontogeny of biochemical pathways in fetal cells using animal models of fetal malnutrition (FM); and (5), to relate neurochemical changes in the brain to later neurosensory and behavioral responses of the FM animal. The collaborative human studies will be carried out at 3 medical centers: Oklahoma University Health Sciences Center, Los Angeles County/University of Southern California, and the Centro Medico Nacional, Instituto Mexicano del Seguro Social in Mexico City. LAC/USC and CMN serve populations at high risk for FM. Nutrient and amino acid studies are achieved by collaboration with USDA Human Nutrition and Protein Nutrition Research Laboratories. The highly integrated study design generates a large number of sequential study variables for each subject, suitable for product moment correlations and multiple regression analyses. Prediction equations are developed from the latter. The initial phase of this program led to equations which could identify mothers at 24 or 32 weeks of gestation whose infants were likely to deviate significantly from their expected birth size based on gestational age and maternal midpregnancy weight, height and age. The prediction equations were developed from maternal leukocyte and nutrient measures. The proposed program is designed to develop, refine, field test and adjust the prediction equations. When this is accomplished, it should be possible to identify mothers at midgestation who will have FM babies. Discrimination between causal factors also should be possible. This will provide the basis to develop specific treatments for mothers early in pregnancy to enhance fetal growth and prevent FM.